Expression of VEGF and its Receptors and Angiogenesis in Bone and Soft Tissue Tumours

6th Saturday, 2012  |   Bone Cancer  |  no comments

Hara H et al. Anticancer Research. November-December 2006 vol.26 no. 6B Pp.4307-11
Tumour angiogenesis and vascularization are essential requirements for the growth and metastasis of tumours. There is evidence that overexpression of the vascular endothelial growth factor (VEGF) is correlated with an adverse prognosis in some tumours. The expression of VEGF, its receptors and microvessel density (MVD) of bone and soft tissue tumours was evaluated. Materials and Methods: Tissue specimens of 60 patients including 30 malignant and 30 benign tumours confirmed by biopsy were examined. Expression of VEGF and its receptors (flt-1 and KDR/flk-1) was observed by immunohistochemistry. Tumour angiogenesis was assessed morphologically by measuring intratumoral MVD. Results: Semi-quantitative evaluation of immunoreactivity showed that VEGF was significantly higher in malignant tumours than in benign tumours. A correlation was found between the immunoreactivity of VEGF and KDR. Moreover, correlations were found either between MVD and VEGF or between MVD and KDR/flk-1. Conclusion: Signal transduction, in particular by VEGF and KDR, potentially contributes to the angiogenesis of bone and soft tissue tumour. Expression of VEGF receptors was reported in a variety of nonendothelial cells, including cancer cells.

Berberine inhibits angiogenic potential of Hep G2 cell line through VEGF down-regulation in vitro.

6th Saturday, 2012  |   Herb or Compound  |  no comments

Jie Sh et al. Journal of Gastroenterology and Hepatology. Volume 26, Issue 1, pages 179–185, January 2011 DOI: 10.1111/j.1440-1746.2010.06389.x
Background and Aim:  Berberine, an herbal alkaloid, has been reported to have promotion potential of apoptosis and anticancer effect on a variety of human tumour cells. To obtain more specific understanding of those consequences of berberine on hepatocellular carcinoma (HCC) and the tumour microenvironment, we conducted in vitro experiments to investigate the inhibitory effect of berberine on tumour-induced angiogenesis using HCC cells and human umbilical vein endothelial cells (HUVECs)
Berberine inhibited the capacity of HCC to stimulate HUVEC’s proliferation, migration and endothelial tube formation, suggesting that berberine could influence the cross-talk between the HCC cell and vascular endothelial cells. These results demonstrate berberine’s antiangiogenesis property and its clinical potential as an inhibitor of tumor angiogenesis. Subsequently analyses reveal that berberine prevents secretion of VEGF from HCC and down-regulates VEGF mRNA expression.
Conclusion:  These findings strongly suggest that berberine is a potential antiangiogenic agent

Inhibitory effect of berberine on the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and matrix metalloproteinase-2

6th Saturday, 2012  |   Lung Cancer  |  no comments

Peng P-L et al. Toxicology and Applied Pharmacology. Volume 214, Issue 1, 1 July 2006, Pages 8-15 doi:10.1016/j.taap.2005.11.010
Berberine, a compound isolated from medicinal herbs, has been reported with many pharmacological effects related to anti-cancer and anti-inflammation capabilities. In this study, we observed that berberine exerted a dose- and time-dependent inhibitory effect on the motility and invasion ability of a highly metastatic A549 cells under non-cytotoxic concentrations. In cancer cell migration and invasion process, matrix-degrading proteinases are required. A549 cell treated with berberine at various concentrations showed reduced ECM proteinases including matrix metalloproteinase-2 (MMP2) and urokinase-plasminogen activator (u-PA) by gelatin and casein zymography analysis. The inhibitory effect is likely to be at the transcriptional level, since the reduction in the transcripts levels was corresponding to the proteins. Moreover, berberine also exerted its action via regulating tissue inhibitor of metalloproteinase-2 (TIMP-2) and urokinase-plasminogen activator inhibitor (PAI). The upstream mediators of the effect involved c-jun, c-fos and NF-?B, as evidenced by reduced phosphorylation of the proteins. These findings suggest that berberine possesses an anti-metastatic effect in non-small lung cancer cell and may, therefore, be helpful in clinical treatment.

Wogonin, a bioactive flavonoid in herbal tea, inhibits inflammatory cyclooxygenase-2 gene expression in human lung epithelial cancer cells

5th Friday, 2012  |   Herb or Compound  |  no comments

Chen L-G et al. Molecular Nutrition & Food Research. Volume 52, Issue 11, pages 1349–1357, November 2008 DOI: 10.1002/mnfr.200700329
Wogonin has been reported to exhibit anticancer and anti-inflammatory properties. Cyclooxygenase-2 (COX-2) is a key enzyme in the production of prostaglandins in inflammatory conditions. In this study, the effect of wogonin on phorbol 12-myristate 13-acetate (PMA)-induced COX-2 expression was investigated. It showed that wogonin inhibited PMA-induced COX-2 protein and mRNA levels in human lung epithelial cancer cells, and the mechanism of this inhibition was at the transcriptional level by using COX-2 gene promoter assay. Among various signal inhibitors, the mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitor U0126 also inhibited PMA-induced COX-2 expression and COX-2 promoter activation. The activity of AP-1-driven promoter, but not nuclear factor-kappa B (NF-?B), was inhibited by U0126. The data indicated that MEK1/2-AP-1 is very important for PMA-induced COX-2 expression. Wogonin also inhibited PMA-induced AP-1 activation and the expression of c-Jun, a key component of AP-1. Taken together, it is suggested that wogonin inhibits PMA-induced COX-2 gene expression by inhibiting c-Jun expression and AP-1 activation in A549 cells.

Protective role of wogonin against lipopolysaccharide-induced angiogenesis via VEGFR-2, not VEGFR-1

5th Friday, 2012  |   Herb or Compound  |  no comments

Lin C-M et al. International Immunopharmacology. Volume 6, Issue 11, November 2006, Pages 1690-1698. doi:10.1016/j.intimp.2006.07.003 Wogonin, one of flavonoid derived from particular plants, enriches the property of anti-inflammation. Inflammation-stimulated angiogenesis plays an important role in many pathological diseases, such as rheumatoid arthritis, atherosclerosis, and cancer. The aim of this study was to investigate the suppressive effect of wogonin on lipopolysaccharide (LPS)-induced angiogenesis in human umbilical endothelial cell (HUVEC) cultures. By cell differentiation assays, migration and tube formation activity under LPS treatment were evaluated. Besides, IL-6 neutralizing antibody was added to test the inhibitory effect in the phenotypic alteration. Western blot analysis, ELISA cytokine assay, and quantitative real time-PCR were performed for VEGF, IL-6, VEGF receptors, and IL-6 receptor gene expressions on HUVEC with wogonin treatment. Furthermore, in vivo chorioallantoic membrane (CAM) assay was applied to evaluate the percentage of new vessels formation. The results revealed that wogonin (10? 8–10? 5 M) inhibited LPS-induced angiogenesis in a concentration-dependent manner. The mRNA and protein expressions of VEGF, VEGFR-2, IL-6, and sIL-6R? were attenuated (P < 0.05), but not VEGFR-1. In the LPS-induced CAM model, our data suggested that wogonin (10? 8–10? 5 M) significantly decreased new vessel formation and vascular network (P < 0.05). We conclude that wogonin suppresses both in vitro and in vivo LPS-induced angiogenesis, through VEGFR-2, but not VEGFR-1